Optimal adjuvant therapy for resected hepatocellular carcinoma: a systematic review with network meta-analysis

Abstract

ObjectivesMajor adjuvant therapies (ATs) for resected hepatocellular carcinoma (HCC) include chemotherapy, internal radiation therapy (IRT), interferon therapy (IFNT) and immunotherapy but the optimum regimen remains inconclusive. We aim to compare these therapies in terms of patient survival and recurrence rates.MethodsWe searched PubMed, EMBASE and Cochrane library databases for randomized trials comparing the above four therapies until 31 March 2014. We estimated the HRs for survival and ORs for overall recurrence among different therapies. Toxic effects were also evaluated.ResultsFourteen eligible articles were included. IFNT improved 5-year survival greatly (HR 1.81, 95% CI 1.01–3.81, P = 0.034), whereas chemotherapy (HR 0.33, 95% CI 0.03–2.02), IRT (HR 0.31, 95% CI 0.02–3.33) and immunotherapy (HR 0.73, 95% CI 0.05–9.12) all provided a poorer survival outcome after 1-year. Similarly, for 5-year survival rates, although differing, IRT did not provide a significant improvement in survival (HR 1.38, 95% CI 0.34–5.19) compared with IFNT. Chemotherapy (HR 0.49, 95% CI 0.18–1.14) and immunotherapy (HR 0.56, 95% CI 0.17–1.59) did not appear to provide benefit over IFNT. Chemotherapy was ranked the worst in overall recurrence (OR 0.99, 95% CI 0.18–5.38) and most likely to cause toxic effects.ConclusionsIFNT was the most efficacious AT regimen both for short and long term survivals. Immunotherapy and IFNT were the most two effective in preventing overall relapse for resected HCC.

Utilization of animal models to investigate nonalcoholic steatohepatitis-associated hepatocellular carcinoma

“…Therefore, it is proposed that TNF-α and NF-κB signaling is involved in ER stress-mediated lipotoxicity and hepatocellular death, as well as further transformation to malignancy [68]. To further support the critical role of ER stress in NASH progression and HCC development, knock-outs of another key protein in a gatekeeper, Gp78, an E3 ubiquitin ligase, which degrades unfolded protein in ER, resulted in up-regulation of unfolded protein response (UPR) pathways and SREBP-1 regulating de novo lipogenesis; the model spontaneously developed NASH, and further progressed to HCC in one year [69]. …”

“…Currently, hepatic carcinogenesis is not fully understood in general, and HCC management strategies are not effective enough to significantly increase 5-year survival rate [69]. Clinical and laboratory research of NASH-associated HCC is in its infancy, and faces tremendous challenges, such as multifactorial features, difficulty in establishing causative-effect links in population studies, and lack of reliable animal models for NASH and NASH-HCC.…”

Statin use is associated with a reduced risk of hepatocellular carcinoma recurrence after initial liver resection

“…Adjuvant therapy has been expected to reduce HCC recurrence and prolong postsurgical survival. Indeed, several drugs including interferon, sorafenib, and acyclic retinoid have been examined to determine their protective effect against HCC recurrence (7)(8)(9)(10). However, effective adjuvant therapies for use after HCC resection have yet to be established.…”

R-spondin 2 promotes proliferation and migration via the Wnt/β-catenin pathway in human hepatocellular carcinoma

“…HCC, characterized by rapid recurrence and poor survival, remains a challenging disease to treat (3). As HCC is not sensitive to radiotherapy or chemotherapy, surgery is the only effective treatment (4). However, the rate of recurrence is high and metastasis is common following surgery, which leads to the poor prognosis for HCC (3).…”